Over the past four years we have made or extended four important discoveries that form the basis for the present proposal: 1) the biosynthesis of basement membrane does not conform to the expected route for glycoproteins; 2) an enzyme that degrades basement in vivo has been discovered and partially characterized; 3) soluble basement membrane has been partially characterized; 4) a pore size has been identified in basement membrane by negative staining. These observations have led to a new concept of basement membrane. It is known to be composed of a tropocollagen core to which is bonded an antigenic glycoprotein. These molecules are arranged as a mesh with a definable pore size. These pores are probably filled with soluble basement membrane, serum protein and or ground substance, and serve as a mechanical filter and the content of the pores probably serve as a chemical barrier or operate on the basis of ion exchange or molecular sieving. Further biosyynthetic studies using morphological and biochemical approaches are proposed; the basement membranases will be further characterized and will be used to make fragments of basement membrane for biochemical analysis. Search will be made for mutant lines of parietal yolk sac carcinoma cells to acquire monoclonal fragments of the molecules for analysis. Soluble basement membrane molecules will be characterized further. The pore size will be measured and the mode of function of soluble and insoluble basement membrane in disease will be determined.